This is a new proposal to identify and study the function of a putative recessive tumor suppressor gene or genes in 3p21.3 important in the development of lung cancers. Evidence for such a tumor suppressor comes from studies showing the early loss of 3p21 alleles in preneoplasia, and allele loss of 3p genes in 70-80% of both small cell and non-small cell lung cancers. In specific aim I it is proposed to clone the gene using a series of resources including a set of homozygous deletions in lung tumor cell lines defining a 350 kb and potentially 30 kb critical region, and a high resolution physical and transcription map with 25 cDNA clones already identified in this region. Specific aim 2 is to determine functional characteristics of this locus by introduction of portions of chromosome 3p into human lung cancer lines bearing a 3p21.3 abnormality, and testing for suppression of tumorigenicity using nude mice, soft agarose culture and studies of apoptosis. In specific aim 3 the applicant plans to follow up on an observation that this region might be involved in suppressing telomerase activity by investigating telomere length and telomerase function in lung cancer cells altered by gene transfer.